Expression of wild-type p53 stimulates an increase in both Bax and Bcl-xL protein content in HT29 cells

• Published in: Oncogene Vol. 13; no. 12; p. 2631
• Main Authors: Merchant, A K, Loney, T L, Maybaum, J
• Format: Journal Article
• Language: English
• Published: England 19-12-1996
• Subjects: Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Blotting, Western; Cell Cycle; HT29 Cells - metabolism; HT29 Cells - pathology; Humans; Phenotype; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2; Temperature; Time Factors; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Up-Regulation
• ISSN: 0950-9232

It has been shown previously that wild-type p53 activity can simultaneously up-regulate Bax, a protein which predisposes cells to programmed cell death (PCD), and down-regulate Bcl-2, a protein which antagonizes PCD. These findings have been interpreted to suggest that correction of the mutant p53 status of some tumor cells may be a means of increasing their sensitivity to chemotherapeutic agents, by increasing their likelihood of undergoing PCD. We show here that when wild-type p53 activity is expressed in HT29 human colon cancer cells by use of a temperature sensitive p53 mutant, Bax levels rise, but so do levels of Bcl-xL protein. These observations indicate that Bcl-2 and Bcl-xL are regulated differently in response to wild-type p53 activity and that, while correction of mutant p53 phenotype may effectively kill cells having Bcl-2 as their major defense against PCD, this is not necessarily the case in cells using Bcl-xL as their primary defense.